Apparatus for handling liquids and a process for operating the device

ABSTRACT

An apparatus for handling liquids and including a lighting installation for lighting an approximately punctiform illumination point in the room, an approximately punctiform light-receiving device having a photodetector for providing a measuring signal dependent on the intensity of the light received, an imaging system for imaging the illumination point onto the approximately punctiform light-receiving device, and an evaluation device for detecting the approaching of an interface between two media of different refractive indices to the illumination point by evaluating the measuring signals provided by the photodetector.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The invention relates to an apparatus for handling liquids and aprocess for operating the device.

[0003] 2. Description of the Prior Art

[0004] An apparatus for handling liquids, in particular, can be anapparatus for proportioning and/or transporting and/or testing and/orprocessing liquids (e.g. chemically, physically or biologically). In theknown apparatuses, operations are performed either manually or in apartially or completely automated manner. Thus, for example, manualpipettes, PC aided proportioning systems, and fully automaticproportioning stations are known for proportioning processes. Fullyautomatic handling stations (so-called “workstations”) are available toproportion, test, and process liquids.

[0005] Both in manual and automatical pipetting, the reception of liquidrequires that the pipette tip be dipped into the liquid, on one hand,but only up to an immersion depth as small as possible, on the other,because the error in proportioning increases with the depth of immersionand the vessel receiving the liquid could be damaged if the pipette tipwas dipped to a large depth. If manual pipettes are employed the userhas to ensure this by accurately checking the depth of pipette tipimmersion. Supervising equipment is used if automatic proportioningdevices are employed.

[0006] Thus, it been known already to use conductive pipette tips orparticularly conductive sensors the approaching of which to the liquidis monitored by a capacity measurement or the dipping of which into theliquid is monitored by a resistance measurement. These solutions,however, are bound to conductive liquids or require that the sensors beat small distances from the liquids or be dipped into them. Conductivepipette tips involve relatively high expenses for the consumablematerial. Inserting specific level sensors into vessels in which theliquid is may be annoying while the samples are processed.

[0007] From WO 0042384 A1, a detection system for liquid levels has beenknown for use in automatic workstations. The system has a light sourceand a photodetector which are directed to the liquid and towards eachother, at an angle. The light source produces a light beam which, whenreflected from the liquid surface, can be detected by the photodetector.The signal outputted by the photodetector varies depending on theintensity of the reflected radiation which is incident thereon. Thisoutput signal, in turn, will vary when the photodetector (and the lightsource) nears the liquid surface in that it increases initially anddecreases afterwards because the reflected light beam travels from oneside to the other side of the photodetector.

[0008] The beam path of the optical system is introduced through theopening of a vessel in which the liquid is. The required angle betweenthe incident beam and the emergent beam limits its use to vessels whichare of a relatively large diameter or a relatively small depth. Invessels having a relatively small diameter or a relatively large depth,however, the beam path would be interrupted at the border of the openingso that a measurement would no longer be possible.

[0009] Accordingly, it is the object of the invention to provide anapparatus for handling samples which makes it more convenient todetermine the location of the liquid level in vessels of a relativelysmall diameter and/or a large depth. It is a further object of theinvention to provide a process for operating an inventive apparatus.

SUMMARY OF THE INVENTION

[0010] The object of the invention is achieved by an apparatus forhandling liquids that has

[0011] a lighting installation for illuminating an approximatelypunctiform illumination point in the room,

[0012] an approximately punctiform light-receiving device having aphotodetector for providing a measuring signal dependent on theintensity of the light received,

[0013] an imaging system for imaging the illumination point onto theapproximately punctiform light-receiving device, and

[0014] an evaluation device for detecting the approach of an interfacebetween two media of different refractive indices to the illuminationpoint by evaluating the measuring signals provided by the photodetector.

[0015] In the inventive device, the approximately punctiformillumination point is imaged onto the approximately punctiformlight-receiving device. As a result, the intensity of the lightradiation received by the light-receiving device will vary and, hence,so will the measuring signal provided by the photodetector if aninterface enters the illumination point between two media of differentrefractive indices. Thus, it can be ascertained whether or not there isan interface in the illumination point. This allows to establish theposition of an interface which can be a liquid level, i.e. the interfacebetween a liquid and air, for example. It further allows to establishthe location of a surface of an object which can be non-covered, forexample, or be covered by a medium transparent to the light of thelighting installation (e.g. a vessel bottom covered with a liquid).

[0016] To determine the position of an interface, it is possible to varythe relative position of the illumination point and the interface untilthe interface is in the illumination point. It further is possible toscan the surface of an object using the illumination point in order tojudge on the position of the entire object and/or its identity on thebasis of individual values or the course of the measuring signal.

[0017] Thus, the inventive apparatus specifically permits to determinethe height of the liquid level in vessels (e.g. reaction vessels and inindentations of microtitration plates), the position and identity ofvessels (e.g. reaction vessels and microtitration plates), and theposition and identity of tools and aids (e.g. pipette tips in a rack).Since the light beam of the lighting installation and the imaging systemare directed coaxially to the illumination point a non-contactingdetection of interfaces is possible from a major distance and at a lowlateral space requirement. This makes it easier to detect the liquidlevel in vessels having a relatively small opening and/or a relativelylarge depth.

[0018] To detect a liquid level free from trouble caused by adjacentvessel walls, it is possible to appropriately use light of a singlewavelength to which a liquid (e.g. water) is opaque.

[0019] The interfaces detectable are both diffusely reflectinginterfaces (e.g. dull surfaces) and substantially directionallyreflecting interfaces (e.g. glossy surfaces or liquid surfaces). Themeasuring signal is particularly strong, above all, for substantiallydirectionally reflecting interfaces if, according to an aspect, thesurface normal line at the place where the interface is scanned by theillumination point is approximately coaxial to the illuminating lightbeam and the optical axis of the imaging system.

[0020] Preferably, the lighting installation comprises a light source ofits own which can be a laser, LED or small bulb, for example.

[0021] The illumination point may be lighted by a linear light beamwhich can be produced by means of a laser, for example. On the linearlight beam, the imaging system will then define a punctiformillumination point, which is imaged onto the approximately punctiformlight-receiving device.

[0022] According to an aspect, the lighting installation also comprisesan imaging system which images the light of a punctiform light sourceonto the illumination point. As a result, the illuminating light beam(or “light bundle”) has its largest intensity in the illumination point.Along with imaging the illumination point onto the light-receivingdevice, this results in a measuring signal which is particularly strong.

[0023] According to an aspect, the light of the punctiform light sourceis fed to the imaging system via a beam splitter and the same imagingsystem images the illumination point onto the light-receiving device viathe beam splitter. This realizes an incident-light measurement. Sincethere is only one imaging system the expenditure involved is relativelylow.

[0024] According to an aspect, the lighting installation has a diaphragmstop and/or an optical waveguide in the optical path of the lightsource, the output of which is formed by the punctiform light source.

[0025] According to an aspect, the light beam lighting the illuminationpoint has an aperture angle of 8° or less so that the light beam isadapted to be introduced into vessels of a relatively small openingdiameter or a large depth without undergoing a fade-out in the externalarea.

[0026] According to an aspect, the distance of the illumination pointfrom the imaging system is 100 mm or more, which enables anon-contacting measurement to be made for the liquid level in manyordinary vessels.

[0027] As a principle, the punctiform light-receiving device may be aphotodetector having a particularly small light-sensitive area.According to an aspect, the punctiform light-receiving device has adiaphragm stop which determines the size of the receiving area.

[0028] According to an aspect, the evaluation device has means forfiltering the measuring signal provided by the photo-detector. Thishelps reduce a noise of the measuring signal and an impact of extraneouslight.

[0029] According to an aspect, the apparatus is an automatic apparatus(e.g. a proportioning station or workstation) for handling liquids. Suchan automatic station allows to control courses therein, e.g. the dippingof pipette tips into vessels, the processing of liquids in certainvessels, etc. because it detects the location and/or identity of liquidsand/or objects.

[0030] According to an aspect, the apparatus has a shifting device todisplace the relative position of the illumination point and theinterface towards the optical axis of the imaging system and/or in across direction thereto.

[0031] The displacement of the relative position of the illuminationpoint and the interface may be caused by the shifting device in variousmanners. According to an aspect, the relative position of the entireoptical system formed by the lighting installation, the imaging system,and the light-receiving device and the interface is adapted to bedisplaced by means of the shifting device. This may be utilized for botha displacement towards the optical axis of the imaging system and adisplacement transverse thereto. To this end, the entire optical systemand/or the interface may be shifted to another place, e.g. by means of aspecimen slide. According to an aspect, the shifting device has a zoomobjective disposed in the imaging system for a displacement towards theoptical axis. For a displacement transverse to the optical axis, theshifting device may have at least one scanning mirror in the imagingsystem.

[0032] According to another aspect, the shifting device is driven by amotor, e.g. for an integration into an automatic apparatus for handlingliquids.

[0033] According to another aspect, the evaluation device controls thedisplacement of the relative position of the illumination point andinterface by the shifting device. Then, displacement may be performeddepending on the measuring signals, e.g. to adjust the illuminationpoint to the interface and/or move it along the interface.

[0034] According to the inventive method for operating an inventivedevice,

[0035] the distance between the illumination point and an interface isvaried, the maximum of the measuring signal is determined while varyingthe distance, and the location of the illumination point is determinedas the location of the liquid level at the maximum of the measuringsignal, and/or

[0036] the illumination point is displaced substantially in parallelwith the interface, individual values or the course of the measuringsignal are determined while the displacement is made, and the positionand/or identity of the interface are determined while referring to thevalues or course of the measuring signal.

[0037] This method allows to determine the location of a liquid leveland/or fixed object and/or the identity of a fixed object. Anidentification of the interface also identifies the liquid or object.

[0038] According to an aspect, the position and/or identity of theinterface are determined by a comparison of the values measured toreference data on the configuration and/or the reflectivecharacteristics of the interface. The reference data may be stored, forexample.

[0039] Finally, according to an aspect, the illumination point isadjusted to a reference surface and the reference signal is measuredthat serves as a reference point for the measuring signal.

BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The invention will be described in more detail below withreference to the accompanying drawings of an embodiment. In thedrawings:

[0041]FIG. 1. shows a roughly schematic structure of an apparatus fordetecting interfaces;

[0042]FIG. 2. shows how to measure a position on a water surface usingdifferent diaphragm stops in a graph with the water surface distanceplotted on the abscissa, the measuring signal on the ordinate, and thediaphragm stop diameter as a curve parameter;

[0043]FIG. 3. shows the maximum signal of the light-receiving devicewhen measuring reflections on various surfaces with the surfacedescription plotted on the abscissa and the measuring signal on theordinate;

[0044]FIG. 4. shows a horizontal scanning of a 384-well microtitrationplate in a graph with the scanning length plotted on the abscissa andthe measuring signal on the ordinate;

[0045]FIG. 5. shows the scanning signal of a bar code in a graph withthe scanning length plotted on the abscissa and the measuring signal onthe ordinate;

[0046]FIG. 6. shows a bar code on an aluminum-coated label which relieson the scanning made in FIG. 5.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0047] Referring to FIG. 1, the apparatus has a light source 1 whichdirects a light beam onto a diaphragm stop 3 or optical waveguidethrough a lens 2.

[0048] Consequently, the aperture 4 of the diaphragm stop 3 or opticalwaveguide forms a punctiform light source from which the light ismirrored onto an imaging optical system 6. The imaging optical system 6which comprises an objective lens focuses the light at a distance z₀.Hence, there is a punctiform illumination point 7 in the focus.

[0049] The imaging optical system 6 images the illumination point 7, viathe beam splitter 5, onto the aperture 8 of a diaphragm stop 9 behindwhich a photodetector 10 is located. The aperture 8 of diaphragm stop 9has the same diameter as has the aperture 4 of diaphragm stop 3.Moreover, the apertures 8, 4 are at the same optical distance from thebeam splitter 5.

[0050] If a diffusely or directionally reflecting surface (with thedirection of the latter being approximately perpendicular to the opticalaxis of the imaging optical system 6) at the illumination pointreflected light passes through the diaphragm stop 9 on the photodetector10. When the entire optical system 11 is moved in the z direction thelight intensity measured by the photodetector 10 will change. It becomesa maximum when the reflecting interface is exactly in the illuminationpoint 7, i.e. at a distance z₀ from the imaging optical system 6.

[0051] Hence, the distance z₀ of an interface or the position of theinterface is determined by scanning in a z direction.

[0052] To detect a liquid surface, the light beam is led into a vesselthrough a vessel opening. If the overall aperture angle of the lightbeam is abt. 8° and the distance z₀ is 100 mm the clear diameter of thevessel opening has to be abt. 14 min if measurement is to be made at adepth z₀ in the vessel.

[0053] While scanning is done in a direction transverse to the opticalaxis of the imaging optical system 6 (x direction) a change in intensityindicates an elevation or depression of the scanned area, but also achange in the degree of reflection.

[0054] The overall aperture angle of the light beam and the diameters ofthe openings 4, 8 of diaphragm stops 3, 9 act on the measuring accuracyof the apparatus. It will become the larger the larger the overallaperture angle is and the smaller the diameter is.

[0055] In an embodiment, the light source 1 is a laser diode having awavelength of 670 manometers which is coupled via a light-transmittingfiber 125 μm in diameter. The diameter of aperture 6 of diaphragm stop 7is abt. 100 μm. A Si photodiode VTB 5051 from EG & G FVCTEC serves as aphotodetector.

[0056]FIG. 2 shows the increase in measuring accuracy with a decreasingdiameter of the diaphragm stop opening while measuring the position of awater surface. The zero of z is chosen at random.

[0057] Since different interfaces reflect differently the height of themeasuring signals covers a wide range. The above-described apparatus wasused to measure the currents shown in FIG. 3 in the maximum of intensityon various interfaces on the photodetector. An object can be identifiedby means of the measuring signals which emanate from various interfacecontained therein.

[0058] In FIG. 4, the current measured on the photodetector 10 is shownscanning the surface of a black microtitration plate having 384 wells.The minima of the current indicate the scanning of a receptacle (aso-called “well”) and the peaks there-between that of the surfaceportions between the receptacles. An evaluation of the measuring signalallows to ascertain that the characteristic dimensions of a 384-wellmicrotitration plate are present. Thus, an automatic device can discoverthat there is a 384-well microtitration plate, and can accommodateproportionings thereto.

[0059] In FIG. 5, the current measured on the photodetector 10 is shownscanning the surface of the bar code which is shown in FIG. 6. Theminima of intensity are associated with the dark stripes and the maximaof intensity are associated with the bright stripes of the bar codehere. This enables an automatic identification of an object which ismarked by bar codes.

What is claimed is:
 1. An apparatus for handling liquids, comprising: alighting installation (1 to 6) for lighting an approximately punctiformillumination point (7) in the room, an approximately punctiformlight-receiving device (9, 10) having a photodetector (10) for providinga measuring signal dependent on the intensity of the light received, animaging system (6) for imaging the illumination point (7) onto theapproximately punctiform light-receiving device (9, 10), and anevaluation device for detecting the approaching of an interface betweentwo media of different refractive indices to the illumination point (7)by evaluating the measuring signals provided by the photodetector (10).2. The apparatus as claimed in claim 1, wherein the light beam lightingthe illumination point (10) and the optical axis of the imaging system(6) are directed approximately coaxially to the illumination point (10).3. The apparatus as claimed in claim 2, wherein the light beam lightingthe illumination point (10) and the optical axis of the imaging system(6) are directed approximately coaxially to the interface.
 4. Theapparatus as claimed in claim 1, wherein the lighting installation (1 to6) comprises a light source.
 5. The apparatus as claimed in claim 4,wherein the light source (1) is a laser, LED or small bulb.
 6. Ameasuring apparatus as claimed in claim 1, wherein the lightinginstallation (1 to 6) also comprises an imaging system (6) which imagesthe light of a punctiform light source (1 to 4) onto the illuminationpoint (10).
 7. The apparatus as claimed in claim 6 wherein the light ofthe punctiform light source (1 to 4) is fed to the imaging system (6)via a beam splitter (5) and the same imaging system (6) images theillumination point (10) onto the light-receiving device (9, 10) via thebeam splitter (5).
 8. The apparatus as claimed in claim 6, wherein thelighting installation (1 to 6) has a diaphragm stop (3) and/or anoptical waveguide in the optical path of the light source (1).
 9. Theapparatus as claimed in claim 1, wherein the light beam lighting theillumination point (10) has an aperture angle of 8° or less.
 10. Theapparatus as claimed in claim 1, wherein the distance of theillumination point (10) from the imaging system (6) is 100 mm or more.11. The apparatus as claimed in claim 1, wherein the punctiformlight-receiving device (9, 10) has a diaphragm stop (9).
 12. Theapparatus as claimed in claim 1, wherein the evaluation device has meansfor filtering the measuring signal provided by the photodetector (10).13. The apparatus as claimed in claim 1, which has a shifting device todisplace the relative position of the illumination point (10) and theinterface towards the optical axis of the imaging system (6) and/or in across direction thereto.
 14. The apparatus as claimed in claim 13wherein the relative position of the optical system (11) formed by thelighting installation (1 to 6), the imaging system (6), and thelight-receiving device (9, 10) and the interface is adapted to bedisplaced by means of the shifting device.
 15. The apparatus as claimedin claim 13, wherein the shifting device has a zoom objective (6) in theimaging system.
 16. The apparatus as claimed in claim 13, wherein theshifting device is driven by a motor.
 17. The apparatus as claimed inclaim 16, wherein the evaluation device controls the displacement of therelative position of the illumination point (10) and interface via theshifting device.
 18. The apparatus as claimed in claim 1, which detectsthe location of liquid levels and/or objects and/or the identity ofobjects.
 19. The apparatus as claimed in claim 18, which detects thelocation of liquid levels in reaction vessels and/or microtitrationplates and/or the location of reaction vessels and/or microtitrationplates and/or pipette tips and/or the identity of reaction vesselsand/or microtitration plates and/or pipette tips.
 20. The apparatus asclaimed in claim 1, which is an automatic apparatus.
 21. The apparatusas claimed in claim 18, which detects objects having optically sensiblemarkings in order to identify them.
 22. A method of operating anapparatus including a lighting (1 to 6) for lighting an approximatelypunctiform illumination point (7) in the room, an approximatelypunctiform light-receiving device (9, 10) having a photodetector (10)for providing a measuring signal dependent on the intensity of the lightreceived, an imaging system (6) for imaging the illumination point (7)onto the approximately punctiform light-receiving device (9, 10), and anevaluation device for detecting the approaching of an interface betweentwo media of different refractive indices to the illumination point (7)by evaluating the measuring signals provided by the photodetector (10),wherein the distance between the illumination point (7) and an interfaceis varied, the maximum of the measuring signal is determined whilevarying the distance, and the location of the illumination point (7) isdetermined as the location of the liquid level at the maximum of themeasuring signal, and/or the illumination point (7) is displacedsubstantially in parallel with the interface, individual values or thecourse of the measuring signal are determined while the displacement ismade, and the position and/or identity of the interface are determinedwhile referring to the values or course of the measuring signal.
 23. Themethod as claimed in claim 22, wherein the position and/or identity ofthe interface are determined by a comparison of the values measured toreference data on the configuration and/or the reflectivecharacteristics of the interface.
 24. The method as claimed in claim 22,wherein the illumination point (9) is adjusted to a reference surfaceand the reference signal is measured.